Journal
NANOMEDICINE
Volume 14, Issue 18, Pages 2409-2422Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/nnm-2018-0496
Keywords
Alzheimer's disease; chitosan nanocapsules; nanomedicine; nasal administration; p38 MAPK
Funding
- 'Ayudas a la Investigacion' BBVA Fundation Grant
- Spanish Ministry of Science [SAF2016-76722, SAF2014-54763-C2-2-R]
- Spanish Ministry of Economy and Competitiveness [SAF2016-76722, SAF2014-54763-C2-2-R]
- Fondo Social de la DGA (grupos DGA)
- Catedra SAMCA (Universidad de Zaragoza)
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Aim: To determine whether a p38 MAPK inhibitor incorporated into nanoemulsion-based chitosan nanocapsules can reduce the activity of this kinase in the brain through their nasal administration in mice. Materials & methods: We selected the p38 MAPK inhibitor PH797804, an ATP-competitive inhibitor of p38 alpha encapsulated in nanoemulsion-based chitosan nanocapsules. Biological effect was evaluated in microglial and neuronal cells in vitro and in ex vivo and in vivo systems, in a mouse model of Alzheimer's disease. Results: Encapsulated inhibitor retains enzymatic inhibitory activity and tissue penetration capacity in vitro, ex vivo and in vivo. Conclusion: Nasal administration of chitosan nanocapsules can be an effective approach for brain-restricted reduction of p38 MAPK activity, thus reducing the side effects of systemic administration.
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